Dose-related behavioral, subjective, endocrine, and psychophysiological effects of the κ opioid agonist Salvinorin A in humans

Biol Psychiatry. 2012 Nov 15;72(10):871-9. doi: 10.1016/j.biopsych.2012.06.012. Epub 2012 Jul 18.


Background: Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA)-a highly selective agonist at the κ opiate receptor-is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans.

Methods: In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological, and endocrine effects of 0 mg, 8 mg, and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia.

Results: SA produced psychotomimetic effects and perceptual alterations, including dissociative and somaesthetic effects, increased plasma cortisol and prolactin, and reduced resting electroencephalogram spectral power. The SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits, or changes in vital signs. The effects were transient and not dose-related. SA administration was very well-tolerated without acute or delayed adverse effects.

Conclusions: SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with κ opiate receptor agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved, and to explore the basis for individual variability in its effects.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Cardiovascular System / drug effects
  • Cognition / drug effects
  • Cross-Over Studies
  • Diterpenes, Clerodane* / administration & dosage
  • Diterpenes, Clerodane* / adverse effects
  • Diterpenes, Clerodane* / blood
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods
  • Electroencephalography / methods
  • Euphoria / drug effects
  • Female
  • Hallucinogens / administration & dosage
  • Hallucinogens / adverse effects
  • Hallucinogens / blood
  • Humans
  • Hydrocortisone / blood
  • Illicit Drugs*
  • Male
  • Perception / drug effects
  • Prolactin / blood
  • Psychiatric Status Rating Scales
  • Psychoses, Substance-Induced* / blood
  • Psychoses, Substance-Induced* / diagnosis
  • Psychoses, Substance-Induced* / physiopathology
  • Psychoses, Substance-Induced* / psychology
  • Receptors, Opioid, kappa / agonists
  • Sensation / drug effects


  • Diterpenes, Clerodane
  • Hallucinogens
  • Illicit Drugs
  • Receptors, Opioid, kappa
  • Prolactin
  • salvinorin A
  • Hydrocortisone